1. Field of the Invention
The present invention relates to coated particles and to methods of making and using them. These coated particles have application in the targeting and release of one or more materials into selected environments, the absorption of one or more materials from selected environments and the adsorption of one or more materials from selected environments.
2. Related Art
Two particle technologies-polymer-coated particles and liposomesxe2x80x94are of general interest.
Polymer-coated particles have been very important in the development of useful microparticles and of controlled-release vehicles generally. In certain circumstances polymers have coating and spreading properties that provide for good encapsulation of various matrices, and they are available in a range of chemistries and molecular weights. Certain polymeric coatings are of such utility and low toxicity that approval has been obtained for their use even in injectable products within the pharmaceutical industry, most notably polylactic-glycolic acid copolymers, and the usefulness of polymeric coatings in oral products is well-established, as in the cases of Eudragits, gelatin, and a number of natural gums. In many settings in fact, microparticle coatings are tacitly assumed to be polymers.
However, polymer-coated particles exhibit several limitations, as the flattened and diffuse response of their polymer coatings to chemical and physical triggers indicates. This is due to two factors. First, the high molecular weight of polymers reduces their diffusion coefficients and their kinetics of solubilization. Second, the neighboring group effect broadens the curves representing the chemical responses to triggers such as, inter alia, pH, salinity, oxidation and reduction, ionization, etc. (The neighboring group effect indicates that chemical changes in one monomeric unit of a polymer significantly alter the parameters governing chemical transitions in each of the neighboring monomeric units.) Further, most polymers are collections of chemical species of broadened molecular weight distribution. In addition, for a given application of the polymer coated particle only a limited number of suitable polymers are frequently available. This is due to a number of factors: regulatory issues: the coating processes often entail harsh chemical and/or physical conditions, such as solvents, free radicals, elevated temperatures, dessication or drying, and/or macroscopic shearing forces needed to form the particles; the limited mechanical and thermal stabilities of the polymeric coatings in industrial applications; and adverse environmental impacts in large scale applications of polymer-coated particles, such as in agricultural use.
Liposomes also exhibit a number of limitations. Among these are their physical and chemical instabilities. The release of a material disposed within the liposome is usually dependent on the destabilization of the structure of the liposome. In particular, the absence of porosity precludes the pore-controlled release of such materials. The dual requirements of 1) physical stability of the liposome until release is desired on the one hand and 2) release of materials by bilayer destabilization when release is desired on the other, are problematic. (The term liposomes is frequently interchanged with the term vesicles and is usually reserved for vesicles of glycerophospholipids or other natural lipids. Vesicles are self-supported closed bilayer assemblies of several thousand lipid molecules (amphiphiles) that enclose an aqueous interior volume. The lipid bilayer is a two-dimensional fluid composed of lipids with their hydrophilic head groups exposed to the aqueous solution and their hydrophobic tails aggregated to exclude water. The bilayer structure is highly ordered yet dynamic because of the rapid lateral motion of the lipids within the plane of each half of the bilayer.) See O""Brien. D. F. and Rarnaswami, V. (1989) in Mark-Bikales-Overberger-Menges Encyclopedia of Polymer Science and Engineering. Vol. 17, Ed. John Wiley and Inc., p. 108.
It is an object of the invention to provide coated particles that are suitable for solubilizing or containing a wide variety of materials, including materials sensitive to physical, chemical or biological deterioration.
It is an object of the invention to provide coated particles that release one or more material disposed within a matrix in their internal cores without requiring the destabilization of that matrix.
It is an object of the invention to provide coated particles covering a wide range of physical and chemical properties, particularly in the selection of the coating, such that a user can substantially preselect the coating and release characteristics.
It is an object of the invention to provide coated particles that sharply initiate the release or absorption of one or more materials to or from a selected environment in response to one or more physical or chemical triggers.
It is an object of the invention to provide a wide variety of coated particle systems that can be tailored to the particular physical, chemical and biological requirements of their contemplated use, such as mechanical and thermal stability in industrial applications of the coated particles or freedom from adverse environmental impact in large scale application of the coated particles in agricultural use.
It is an object of the invention to provide coated particles that provide, if desired, a porous coating that permits pore-controlled release of material disposed within them or pore-controlled absorption of materials disposed without them.
It is a further object of the invention to provide coated particles that can incorporate targeting moieties such as antibodies, lectins, receptors, and complementary nucleic acids, for targeting the particles to specific sites, either before or after the coating releases, as well as other bioactive materials such as absorption enhancers, adjuvants, adsorption inhibitors, or pharmaceutical actives themselves.
It is a further object of the invention to provide coated particles that can be produced by a process that is flexible and can be adapted to a wide range of actives, coatings, and matrices.
It is a further object of the invention to provide coated particles that have a polymerized interior matrix which is more permanent chemically, thermodynamically, and structurally than their unpolymerized counterparts.
It is a still further object of the invention to provide coated particles that can be made by a simple process, including, preferably, without entailing harsh physical and/or chemical conditions.
The foregoing and other objects are provided by a coated particle that comprises an internal core comprising a matrix and an exterior coating. The matrix consists essentially of at least one nanostructured liquid phase, or at least one nanostructured liquid crystalline phase or a combination of the two and the exterior coating comprises a nonlamellar material that is a nonlamellar crystalline material, a nonlamellar amorphous material, or a nonlamellar semi-crystalline material.
In a preferred embodiment, the coated particle may be made by
1. providing a volume of the matrix that includes at least one chemical species having a moiety capable of forming a nonlamellar material upon reaction with a second moiety and
2. contacting the volume with a fluid containing at least one chemical species having the second moiety under nonlamellar solid material-forming conditions so as to react the first moiety with the second moiety, and subdividing the volume into particles by the application of energy to the volume, or performing this subdivision into particles before, and/or after, the chemical reaction.
Alternatively, the coated particle can be made by one of the following processes:
providing a volume of the matrix that includes a material in solution in it that is capable of forming a nonlamellar material that is insoluble in the matrix and causing the aforesaid material to become insoluble in the matrix and subdividing the volume into particles by the application of energy to the volume;
dispersing particles of said matrix into a fluid that includes at least one chemical species having a moiety capable of forming a nonlamellar material upon reaction or association with a second moiety and adding to said dispersion at least one chemical species having said second moiety to react said first moiety with said second moiety;
dispersing particles of said matrix into a fluid that includes at least one chemical species having a moiety capable of forming a nonlamellar material upon reaction or association with a second moiety, adding to said dispersion at least one chemical species having said second moiety to react said first moiety with said second moiety, and subdividing the resulting material into particles by the application of energy to said material;
dispersing a volume of said matrix in a form of said nonlamellar material selected from the group consisting of liquefied form, solution, or fluid precursor, and solidifying said nonlamellar material by a techniques selected from the group consisting of cooling, evaporating a volatile solvent, or implementing a chemical reaction; or
dispersing or dissolving a volume of said matrix in a liquid comprising said nonlamellar material in solution or dispersed form and comprising also a volatile solvent, and spray-drying said solution or dispersion.
Or, a combination of these methods can be applied.